{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:19:49Z","timestamp":1790687989576,"version":"4.1.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kao Research Council for the Study of Healthcare Science","award":["C93102"],"award-info":[{"award-number":["C93102"]}]},{"name":"2021 Tokai University School of Medicine Research Aid grant","award":["210049"],"award-info":[{"award-number":["210049"]}]},{"name":"Tokai University Research Organization Grant","award":["21NS331825"],"award-info":[{"award-number":["21NS331825"]}]},{"name":"Ohyama Health Foundation Inc.","award":["113"],"award-info":[{"award-number":["113"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21ck0106701h0001"],"award-info":[{"award-number":["21ck0106701h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Immunosenescence refers to the development of weakened and\/or dysfunctional immune responses associated with aging. Several commensal bacteria can be pathogenic in immunosuppressed individuals. Although\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    is a commensal bacterium that colonizes human mucosal surfaces, the gastrointestinal tract, and the oropharynx, it can cause serious infectious diseases, such as pneumonia, urinary tract infections, and liver abscesses, primarily in elderly patients. However, the reason why\n                    <jats:italic>K<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    is a more prevalent cause of infection in the elderly population remains unclear. This study aimed to determine how the host\u2019s intestinal immune response to\n                    <jats:italic>K<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    varies with age. To this end, the study analyzed an\n                    <jats:italic>in vivo K<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    infection model using aged mice, as well as an\n                    <jats:italic>in vitro K<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    infection model using a Transwell insert co-culture system comprising epithelial cells and macrophages. In this study, we demonstrate that growth arrest-specific 6 (Gas6), released by intestinal macrophages that recognize\n                    <jats:italic>K<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    , inhibits bacterial translocation from the gastrointestinal tract by enhancing tight-junction barriers in the intestinal epithelium. However, in aging mice, Gas6 was hardly secreted under\n                    <jats:italic>K<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    infection due to decreasing intestinal mucosal macrophages; therefore,\n                    <jats:italic>K<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    can easily invade the intestinal epithelium and subsequently translocate to the liver. Moreover, the administration of Gas6 recombinant protein to elderly mice prevented the translocation of\n                    <jats:italic>K<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    from the gastrointestinal tract and significantly prolonged their survival. From these findings, we conclude that the age-related decrease in Gas6 secretion in the intestinal mucosa is the reason why\n                    <jats:italic>K<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    can be pathogenic in the elderly, thereby indicating that Gas6 could be effective in protecting the elderly against infectious diseases caused by gut pathogens.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011139","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T13:21:53Z","timestamp":1686230513000},"page":"e1011139","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Gas6 ameliorates intestinal mucosal immunosenescence to prevent the translocation of a gut pathobiont, Klebsiella pneumoniae, to the liver"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-4475","authenticated-orcid":true,"given":"Hitoshi","family":"Tsugawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuto","family":"Ohki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Tsubaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juntaro","family":"Matsuzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuto","family":"Hozumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ppat.1011139.ref001","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.3389\/fimmu.2019.02247","article-title":"Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? 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